Diabetes type I (insulin dependent) patients are required to frequently test their blood glucose levels. In 1993, a ten year long diabetes care and complications trial (DCCT) showed that the preferred mode of treatment of insulin dependent diabetes (Type 1) was by frequent small-dose administrations of insulin to such patients and determining the glucose level after each such administration. To follow such a treatment, a diabetic patient is required to puncture his skin and obtain a drop of blood for the glucose test at least three times a day. Such a frequent and repetitive puncturing is painful and often results in infection and formation of hard scar tissue and as a result, many diabetic patients neglect to sufficiently test their glucose level.
In an attempt to minimize the harm and pain caused by skin puncturing to obtain a blood specimen, alternative methods have been developed. Those methods generally belong to one of the following approaches:                (a) Non-invasive techniques, which are based on the analysis of transmission, scattering or reflectance spectra of various radiations, such as infra-red, photoacoustic and di-electric radiation, which permeate through the skin or other tissues.        (b) Minimally invasive techniques, which are based on drawing out minute specimens of blood or other fluids (sometimes referred to as “interstitial fluid”), in a manner which causes minimal pain or damage, or none at all.        
Guy and Rao (U.S. Pat. No. 5,362,307) have shown a method for determining the concentration of an inorganic or organic substance in an individual by obtaining an interstitial fluid sample from the individual by a process called iontophoresis. In accordance with this method, an electric field is employed, causing the transdermal migration of ions, which carry with them non-charged molecules, such as glucose. This method was recently developed into the GlucoWatch™ product, by Cygnus, Inc., Redwood City, Calif., USA.
Methods for the extraction of glucose and other analytes from the skin, employing chemicals, called “enhancers” or “permeators” (herenafter “permeation enhancers”) were recently described. Aronowitz and Mitchen (PCT WO99/1336) employ a gel, containing propylene glycol. The extracted fluid enters a gel and the concentration of glucose or any other analyte, is determined by a calorimetric reaction. Brown and Edelman (WO99/67645) also use a gel, containing pyrrolidone compounds and optionally other enhancers, to extract the analytes of interest from the skin. Both approaches require placement of gel on the skin for a defined length of time, which extends to more than 10 minutes, in order to ensure sufficient quantity of analyte, which will reflect the concentration of the same analyte in the blood.
Another minimally invasive method for obtaining a body fluid is that of SpecRx, Inc. Norcross, Ga., USA. A minute and shallow round hole is created in the skin, extending just below the stratum corneum and a sample of interstitial fluid is collected through this hole. That fluid is then tested for its glucose content by one of the methods known in the art.
In such minimally invasive methods the concentration of the tested substance in the obtained interstitial fluid sample may not always correctly indicate the level of the same substance in the blood of the tested individual at the time in which the sample was obtained or shortly thereafter. This is mostly due to the fact that the concentration of the tested substance varies in different locations in the body and at different hours of the day. Moreover, although such minimally invasive methods attempt to reduce the pain and damage normally associated with blood sampling, they still often result in discomfort to the tested individual, and involve skin irritation and damage.
Attempts to detect the correct glucose level in the blood by determining the level of glucose in fluids of body samples other than blood such as saliva, urine or tears were found to be non suitable since the concentration of the glucose in such fluids was shown to be variable and, more often than not, did not directly reflect the concentration of the glucose in the blood at the relevant point in time (Sönsken, Patrick et al, Forbat et al, Ben-Aryeh et al, Doneen et al.).